Metformin for treatment of antipsychotic-induced weight gain in a South Asian population with schizophrenia or schizoaffective disorder: A double blind, randomized, placebo controlled study

Atypical antipsychotics are very well known for causing weight gain in patients. However, patients are usually dependent on these medications for the sake of their daily function, so discontinuing treatment because of weight gain is not an option. One way to alleviate this side effect is to use a medication that would cause weight loss in conjunction with using the antipsychotic. One commonly used drug that is known to cause weight loss is metformin. This study looks into the effectiveness of metformin as a weight loss agent when used with an atypical antipsychotic, with a particular focus on South Asian patients for some reason.

The study showed that metformin is an effective weight loss agent when used with an atypical antipsychotic. Patients often lost the weight that they gained from taking the antipsychotic, but they did not lose an unsafe amount of weight. It canceled out the weight gained by taking the antipsychotic while still keeping the patient very safe in all respects.

This study shows that creative drug therapies can be used to optimize the patient experience.

de Silva VA, Dayabandara M, Wijesundara H, et al. Metformin for treatment of antipsychotic-induced weight gain in a South Asian population with schizophrenia or schizoaffective disorder: A double blind, randomized, placebo controlled study. J Psychopharmacol. 2015: 29(12): 1255-1261


Effect of Metformin Added to Insulin on Glycemic Control Among Obese Adolescents with Type 1 Diabetes

Studies currently show that 24% of children and adolescents with Type 1 Diabetes are overweight and 15% are obese. The need for high doses of insulin may further promote weight gain. Additionally, insulin resistance has been associated with increased risk for cardiovascular risk factors. Metformin lowers glucose and was associated with low insulin doses without having an effect on A1C.

A trial was conducted using patients aged 12 to 19 diagnosed with Type 1 Diabetes for at least one year who had an insulin pump or administered at least 3 injections of insulin each day. The patients had an A1C between 7.5% and 9.9% and were in the 85th percentile for BMI. The patients were given 500 mg of metformin that was titrated over 4 weeks to reach 2000mg daily. The rest of the patients were given a placebo.

The baseline A1C was 8.8% in each both groups. At 13 weeks, the mean change in the metformin group was -0.2% and 0.1% in the placebo group. However at 26 weeks, the mean change in the metformin group was 0% and 0.3% in the placebo group. There was no significant difference for glycemic control. However, the patients in the metformin group used less insulin throughout the 26 weeks than the patients on the placebo and more patients in the metformin group maintained or lost weight.

In conclusion, metformin did not improve glycemic control in children or adolescents with Type 1 Diabetes. A few outcomes were favored but not significantly. Additionally, taking metformin increases the risk of GI adverse effects. Therefore, it is not indicated to prescribe metformin to this patient population.

This is interesting because many people do not fully understand the difference between Type 1 and Type 2 Diabetes and the medications to treat each. It is important to know what medications are indicated for each to educate children and parents. Thoughts on another oral medication that may be better suited for this patient population?

JAMA. 2015;314(21):2241-2250. 

Effects of metformin in adolescents with polycystic ovary syndrome undertaking lifestyle therapy: a pilot randomized double-blind study

In an article published by Ladson, et al. the effects of metformin on adolescents with polycystic ovary syndrome (PCOS) were studied. PCOS is a disorder that causes irregular menstruation, increased levels of testosterone, and very often metabolic issues in females of reproductive age. These metabolic issues can lead to increased rates of obesity and diabetes.

The study was looking to see if metformin is an effective treatment for PCOS. Two groups of adolescent females were gathered and educated about lifestyle interventions they could make in order to help cope with their disorder, such as improving diet and increasing exercise. One group was then given increasing doses of metformin, while the other was given a placebo. At the end of the study, the metformin group showed no major difference from the placebo group other than decreased levels of serum testosterone and an increased number of adverse effects. They recommended that metformin not be used to treat adolescents with the disorder.

I feel that this article is important to pharmacy because it deals with off label usage of a drug. Metformin is well known to be indicated for type 2 diabetes, but it has been shown to be useful for other disorders. I think that it is imperative as pharmacists that we try and research studies like these in order to learn about drugs that may be helpful in treating a disorder it is not originally intended for. Although this article recommended not using metformin on PCOS in adolescents, I have read other articles that have highly suggested that adult females with PCOS be put on metformin therapy. What do you think? Should one study like this stop a drug from being used off label?

Link to the article

Ladson, Gwinnett, William C. Dodson, Stephanie D. Sweet, Anthony E. Archibong, Allen R. Kunselman, Laurence M. Demers, Peter A. Lee, Nancy I. Williams, Ponjola Coney, and Richard S. Legro. “Effects of Metformin in Adolescents with Polycystic Ovary Syndrome Undertaking Lifestyle Therapy: A Pilot Randomized Double-blind Study.” Fertility and Sterility 95.8 (2011): n. pag. Clinical Key. Web. 25 Feb. 2016.

Metformin vs. Insulin Treatment in Gestational Diabetes: Developmental Outcomes

Gestational diabetes has been primarily treated with insulin, which does not cross the placental barrier. However, the use of metformin, which does cross the placental barrier, to treat gestational diabetes is becoming increasingly more common. The researchers in this study aim to examine the offspring of these women treated with either insulin or metformin during their pregnancy, and compare the safety of these two treatment methods.

The study design was a prospective follow-up study, involving children whose mothers had been treated for gestational diabetes with either metformin for gestational diabetes. In the original trial, 751 women from either Australia or New Zealand were participants who were randomly assigned to either insulin or metformin to treat their gestational diabetes. 373 of these women were assigned to take metformin, while 378 were assignment to take insulin. The mothers in this study had consented to be contacted for follow-up after their child’s second birthday. The final number of children included in this follow-up study was 211. The children in the study were evaluated using the Bayley Scales of Infant Development (BSID-II), which consists of three different elements: the Mental Developmental Index (MDI), the Psychomotor Developmental Index and the Behaviour Rating Scale (BRS).

The results of this study concluded that there was no significant difference between the developmental outcomes of children whose mothers had been treated with insulin vs. those whose mothers had been treated with metformin for gestational diabetes. The researchers in the study acknowledge that long-term developmental outcomes have not been studied, and should be in order to get a better idea of the long-term safety of these medications for gestational diabetes.

This study is important because it offers a possible different treatment option for women with gestational diabetes. People typically don’t enjoy giving themselves injections, so with metformin as an option, they won’t have to deal with the needles associated with insulin.

Wouldes TA, Battin M, Coat S, Rush EC, et al. Neurodevelopmental outcome at 2 years in offspring of women randomised to metformin or insulin treatment for gestational diabetes. Arch Dis Child Fetal Neonatal Ed. doi:10.1136/archdischild-2015-309602. (Published 24 February 2016).

Metformin Treatment of Antipsychotic-Induced Dyslipidemia: An Analysis of Two Randomized, Placebo-Controlled Trials

Schizophrenic patients on antipsychotic medications tend to experience the adverse effect of dyslipidemia. At this time, no effective treatments have been established to treat this adverse effect. As a result, data was pooled from two randomized, placebo-controlled trials.  201 schizophrenic patients that experience antipsychotic-induced dyslipidemia were either given 1000 mg of metformin to take each day for 24 weeks, or a placebo.

After the 24 week period, the mean difference in the LDL values between individuals receiving metformin and those receiving the placebo treatment decreased by 1.02 mmol/L. Only 25.3% of patient in the metformin group had LDL levels greater than or equal to 3.37 mmol/L, while 64.8% of those in the placebo group had LDL levels greater than or equal to that. It is evident that metformin is effective in reversing antipsychotic-induced dyslipidemia. This study also showed that metformin helped people on antipsychotics lose weight, lowered their total cholesterol and triglyceride levels, and increased their HDL levels. Additionally, insulin resistance can be induced by antipsychotics, and metformin would help with this as well.

After reading about this study, I am wondering whether automatically putting schizophrenic patients on metformin as well as antipsychotics should become the normal protocol. Should this happen, or should we as pharmacists monitor their cholesterol and insulin levels while they are on antipsychotics and only suggest they begin metformin if they exhibit any of the aforementioned adverse effects? If we do put these patients on metformin,  how should we counsel and monitor them?

Mol. Psychiatry. 2016 Jan 26;doi:10.1038/mp.2015.221.